How immune system maintains a memory

The research, published inThe EMBO J, identifies one way in which the immune system is able to provide a quick and successful response to infections like flu or cold that the body has previously encountered, ensuring that long term immunity is built up.

The team demonstrated that a single cycle of activation of the T cells within the immune system leaves behind imprints in the chromosomes within these immune cells. This imprinting occurs at the genes that need to be switched back on as soon as immune cells are reactivated. They propose that this forms the basis of a long-term memory which allows for an immediate response when the body encounters an infection and T cells are activated for a second time.

Rather than immune cells remaining 'switched on' permanently to fight infection continuously, they return to a dormant state but are altered by the initial infection and remain in a partially active state primed to combat any recurrence.

Researchers demonstrate that the first steps in the acquisition of T-cell memory occurred during the initial activation phase of naïve T cells by an antigenic stimulus. This event initiated extensive chromatin remodeling that reprogrammed immune response genes toward a stably maintained primed state, prior to terminal differentiation.

Activation induced the transcription factors NFAT and AP-1 which created thousands of new DNase I-hypersensitive sites (DHSs), enabling ETS-1 and RUNX1 recruitment to previously inaccessible sites. Significantly, these DHSs remained stable long after activation ceased, were preserved following replication, and were maintained in memoryphenotype cells.

Authors show that primed DHSs maintain regions of active chromatin in the vicinity of inducible genes and enhancers that regulate immune responses.

Being able to silence the immune system until it is required to fight infection is also vitally important, else there would be a risk of damaging cells that are part of the host. If this tight control breaks down then it can be the cause of a number of inflammatory or autoimmune disorders, when healthy cells are targeted as if they were foreign.

The author explained, "The initial immune response switches on certain regions within chromosomes of previously inactive T cells to leave them in a more open structure so that they can then sit poised, ready to respond much faster when activated again in the future."